The long-term objectives of this proposal are to examine hormonal mechanisms that may regulate weight loss and weight maintenance induced by bariatric surgery and implantable gastric stimulation (IGS). Particular focus is on hormones of the gut-central nervous system axis that are involved in appetite regulation, gut motility, energy partitioning and energy ZV expenditure. The objectives of Aim One are: a) to compare the changes in both fasting and post-prandial concentrations of ghrelin (total and octanoylated) and peptide YY (PYY) before and after Roux-en-Y gastric bypass (GBP) and gastric banding (BND) in a long-term prospective study and determine if these changes correlate with hunger, satiety, degree of weight loss weight maintenance; b) to characterize and; the fasting and post-prandial concentrations using high performance liquid chromatography of the two molecular forms of PYY, PYY(l-36) and PYY(3-36), in relation to body weight and weight reduction after GBP and BND; and c) to determine if there are differences in plasma leptin per unit fat mass and body composition, particularly visceral fat mass, using nuclear magnetic resonance imaging in weight-reduced individuals after GBP and BND procedures. Aim Two compares metabolic and neuroendocrine changes in individuals GBP and END. The purposes of this who have lost an equivalent amount of weight by calorie restriction, Aim are: a) to determine the role of the foregut in mediating insulin sensitivity through the use of intravenous glucose tolerance tests with frequent blood sampling; and b) compare the effects on thyroid and growth hormone axes with these three weight loss modalities. The focus of Aim Three is to elucidate possible hormonal mechanisms for weight loss induced by the IGS system, a new modality of weight loss therapy currently under investigation. The ultimate goal is to use information from these studies for the development of obesity treatments that are less invasive than bariatric surgery and more effective than current pharmacotherapy.